Perhaps the key to understanding stress pathology lies in consideration of context. In depression, for example, physiological and behavioral symptoms, e.g., helplessness, anhedonia, HPA axis dysfunction and cardiovascular pathology, all mimic those induced by chronic stress regimens in animal models. The key difference between the two is the context in which these responses occur: as argued above, these behaviors and physical reactions may be entirely appropriate when an animal (or person) is confronted with environmental or physical adversity. In human depressives, the link with “actual” stress is less evident, raising the possibility that processes underlying the disorder essentially permit stress related behaviors and physical reactions to occur in the absence of threat. In depressed patients, the prefrontal cortex and amygdala, two critical components of stress circuitry, show abnormal activation patterns without any clear threat present (Drevets, 2000; Mayberg et al., 2005), suggesting the potential for engagement of responses out of context. Mounting situationally inappropriate stress responses may in turn contribute to cumulative damage associated with maladaptive aspects of stress responses (e.g., excess glucocorticoid action).
